1. Field of the Invention
The present invention relates generally to the field of sensors, and more particularly relates to sensors including methods for detecting analytes in fluids.
2. Description of the Prior Art
Sensors are widely used in the technology of detecting analytes present in fluids. The following references are pertinent to this field of art:                1. U.S. Pat. No. 4,887,455 issued on Dec. 19, 1989 to Payne et al. for “Gas Sensor” (hereafter “the '455 Payne patent”);        2. U.S. Pat. No. 5,571,401 issued on Nov. 5, 1996 to Lewis et al. for “Sensor Arrays for Detecting Analytes in Fluids” (hereafter “the '401 Lewis patent”);        3. U.S. Pat. No. 6,319,724 issued on Nov. 20, 2001 to Lewis et al. for “Trace Level Detection of Analytes Using Artificial Olfactometry” (hereafter “the '724 Lewis patent”);        4. Payne, et al., “High-Frequency Measurements of Conducting Polymers: Development of A New Technique for Sensing Volatile Chemicals”, Meas. Sci. Technol. 6 (1995) pp. 1500-1507 (hereafter “the Payne Publication”);        5. Nagle, H. T., et al., “The How And Why Of Electronic Nose”, IEEE Spectrum, September 1998, pp. 22-34 (hereafter “the Nagle Publication”);        6. Baltes, H., et al., “The Electronic Nose In Lilliput”, IEEE Spectrum, September 1998, pp. 35-38 (hereafter “the Baltes Publication”);        
7. U.S. Pat. No. 6,631,333 issued on Oct. 7, 2003 to Lewis et al. for “Methods For Remote Characterization Of An Odor” (hereafter “the '333 Lewis patent”, in addition to U.S. Pat. No. 7,359,802 issued on Apr. 15, 2008 to the same inventors, which is a Divisional patent of the '333 Lewis patent);                8. U.S. Pat. No. 7,465,425 issued on Dec. 16, 2008 to Sun for “Sensor And Method For Detecting Analytes In Fluids” (hereafter “the '425 Sun patent”); and        
9. U.S. Pat. No. 7,696,363 issued on Apr. 13, 2010 to Sun for “Sensor And Method For Detecting Analytes In Fluids” (hereafter “the '763 Sun patent”).
The '455 Payne patent discloses a gas sensor that has a semiconductive organic polymer layer exposed to a gas to be detected. An analyzer applies an alternating electric signal at specific resonant frequencies to the sensor for detecting the change in the sensor's impedance characteristics which is compared by a microcomputer with reference characteristics stored in a memory of the microcomputer. The gas in contact with the sensor can be detected because of the resulting difference spectra of its impedance characteristics. The patent further discloses that the best performance of the invention is likely to be conducted with frequencies ranging 100 MHZ to 500 MHZ where the resonance may happen.
The '401 Lewis patent discloses arrays of chemical sensors, including polymer carbon powder based chemiresistors for detecting analytes in fluids. The sensor include first and second conductive elements electrically coupled to and separated by a chemically sensitive resistor which provides an electrical path between the conductive elements. The resistor includes a plurality of alternating nonconductive regions made of a nonconductive organic polymer and conductive regions made of a conductive material transverse to the electrical path. The resistor further provides a difference in resistance between the conductive elements when contacted with a fluid containing a chemical analyte at a first concentration, and then at a second different concentration. Arrays of such sensors are constructed with at least two sensors having different chemically sensitive resistors providing differences in resistance. Variability in chemical sensitivity from sensor to sensor is provided by qualitatively or quantitatively varying the composition of the conductive and/or nonconductive regions. An “electronic nose” for detecting an analyte in a fluid may be constructed by using such arrays in conjunction with an electrical measuring device electrically connected to the conductive elements of each sensor.
The '401 Lewis patent discloses arrays of chemical sensors, including polymer carbon powder based chemiresistor for detecting analytes in fluids. The sensors include first and second conductive elements electrically coupled to and separated by a chemically sensitive resistor which provides an electrical path between the conductive elements. The resistor includes a plurality of alternating nonconductive regions made of a nonconductive organic polymer and conductive regions made of a conductive material transverse to the electrical path. The resistor further provides a difference in resistance between the conductive elements when contacted with a fluid containing a chemical analyte at a first concentration, and then at a second different concentration. Arrays of such sensors are constructed with at least two sensors having different chemically sensitive resistors providing differences in resistance. Variability in chemical sensitivity from sensor to sensor is provided by qualitatively or quantitatively varying the composition of the conductive and/or nonconductive regions. An “electronic nose” for detecting an analyte in a fluid may be constructed by using such arrays in conjunction with an electrical measuring device electrically connected to the conductive elements of each sensor.
The '724 Lewis patent discloses a method using artificial olfactometry for detecting the presence of an analyte indicative of various medical conditions, including halitosis, periodontal disease and other diseases.
The Payne Publication discloses the change in the alternating current (AC) impedance characteristics of poly-N-(2-pyridyl) pyrrole in the presence of different volatile chemicals.
The Nagle Publication is a special report, which summarizes research and development of the electronic nose instrument through 1990's. The report in detail introduces types of sensors including the respective sensing mechanisms for metal oxide thin film resistor sensors, conductive polymer sensors, polymer coated quartz crystal microbalance (QCM) sensors, polymer coated surface acoustic wave (SAW) sensors, metal-oxide-silicon field-effect-transistor (MOSFET) sensors, dye coated optical fiber (DCOF) sensors, gas chromatography (GC), light spectrum, and mass spectrometry (MS). The report also discloses advantages and disadvantages according to the respective sensors including the sensing mechanisms, wherein a high sensitivity to humidity is addressed as the disadvantage of the polymer film based sensors.
The Baltes Publication reports the developed micronose integrated circuit sensor CMOS chip coated with polymer films according to mechanisms of sensing mass change and dielectric constant change of the polymer films when they load up on volatile organic compounds.
The '333 Lewis patent discloses compositions and systems useful in remote monitoring of chemical hazards, air quality and medical conditions. For example, robotic systems search for and detect explosives, mines, and hazardous chemicals. In addition, the methods, systems and compositions of the invention provide the ability to mine data from database containing a plurality of chemical fingerprints. The patent also summarizes techniques for constructing sensors as disclosed in the Nagle Publication, in addition to a dye-impregnated bread (DIB) arrays and micromachined cantilever (MMC) arrays. The patent further discloses the invented electrically conductive sensor that comprises alternating regions of a conductive material and a material compositionally different than the conductive material between two conductive leads wherein said sensor provides an electrical path through the regions of conductive material and the regions of the compositionally different material.
It can be seen from the above cited references that significant efforts have been devoted in the past for researching and developing configuration of sensors. This is because the configuration of the sensors predominantly governs sensor performance for detecting and identifying analytes in fluids. Specifically, identification of analytes in fluids is accomplished through applying sensors which mimic mechanisms of the mammalian olfactory system that applies probabilistic repertoires of many different receptors to record a single odorant. Having such sensor technologies in conjunction with existing technologies in electrical engineering including highly integrated circuit chips (ICs), advanced softwares, the current sensor technologies improve convenience in detection and identification of analytes.
It is well known that, from studying the mammalian olfactory system, identification of the odorant is dependent upon not only the results from highly specific receptors but also the output from less specific ones. In other words, identification is based on recognizing a spectrum of signals that resemble a specific pattern. Following this direction, conventional technologies in sensor configuration are developed according to the following two schemes to generate a signal spectrum: applying strategies of a multiple sensor configuration and a single sensor configuration.
In the approaches that utilize the multiple sensor configuration, which are disclosed by the Nagle Publication in addition to the '333 Lewis patent, various detecting devices have been developed that use metal oxide thin film resistor sensors, conductive polymer or polymer carbon powder composite film chemi-resistor sensors, QCM, SAW, MOSFET and DCOF sensors, and DIB and MMC arrays. However, although much progress has been made in the past, there are still primary disadvantages inherited from the sensing mechanisms of such multiple sensor technologies. The disadvantages include the requirement of a large number of sensors to generate a patterned information, the sophistication of the sensor configuration, thus the resulting poor reproducibility in sensor manufacturing, the strong humidity influence applying polymer film modified sensors on chemical analysis, the slow response, the expensive electronic equipment required, and the very restricted operating conditions.
In the approaches that utilize the multiple sensor configuration, which are disclosed by the Nagle Publication in addition to the 333 Lewis patent, various detecting devices have been developed that use metal oxide thin film resistor sensors, conductive polymer or polymer carbon powder composite film chemi-resistor sensors, QCM, SAW, MOSFET and DCOF sensors, and DIB and MMC arrays. However, although much progress has been made in the past, there are still primary disadvantages inherited from the sensing mechanisms of such multiple sensor technologies. The disadvantages include the requirement of a large number of sensors to generate a patterned information, the sophistication of the sensor configuration, thus the resulting poor reproducibility in sensor manufacturing, the strong humidity influence applying polymer film modified sensors on chemical analysis, the slow response, the expensive electronic equipment required, and the very restricted operating conditions.
Various polymer films with a general thickness of several micrometers have been extensively used in the multiple sensor configuration to improve sensor sensitivity and detection limit. This is primarily due to the fact that the polymer films can trap including adsorb and absorb analytes of the respective chemicals, according to their specific chemical selectivities on the analytes. As a result, the analytes will be concentrated on the surface or inside of the polymer films prior to detection.
However, the conventional polymer films also inherit a number of disadvantages. First, the thin films of polymer are sensitive to the humidity associated with analytes. Humidity is the predominant factor to influence performance of the polymer film based gas sensors. Second, polymer films have an aging effect that affects the sensor stability for long term usages. Third, it is difficult to achieve reproducibility of the polymer films used in sensors, particularly in a situation when a large number of the sensors must be used in the multiple sensor configuration.
In the approaches for a single sensor configuration also disclosed by the Nagle Publication, various instruments have been developed that are based on the mechanisms of GC, MS, and light spectrum. Generally, these instruments are very expensive. Moreover, they are typically very bulky in size, which makes their miniaturization almost impossible. As a result, they are less attractive in the market, where portability of the instruments becomes increasingly important.
For example, a strategy of point-of-care (POC) is becoming an urgent demand in the field of medical diagnoses. Under the strategy POC, patient healthcare including medical diagnoses are directly conducted at the patients' bedsides of the respective patients' homes. Therefore, medical instruments are advantageous if they are completely portable. In fact, instruments having portabilities are critical in many fields besides the medical field, including security, military and industrial fields.
As an example utilizing the single sensor configuration, the Payne Patent and Payne Publication cited above disclose application of a single sensor for detecting the presence of gaseous analytes from detecting impedance and phase sensitive components of conductive polymer modified electrodes at specific frequencies, where electrical resonant signals are established due to interaction of analytes to the conductive polymer film. However, the Payne device requires high frequencies ranging from 100 MHz to 500 MHz, where the resonance may occur. The high frequency brings significant difficulties in sensor manufacturing and application. In addition, it still has the disadvantages inherent from polymer films.
As an example utilizing the single sensor strategy, the Payne patent and Payne Publication cited above disclose application of a single sensor for detecting the presence of gaseous analytes from detecting impedance and phase sensitive components of conductive polymer modified electrodes at specific frequencies, where electrical resonant signals are established due to interaction of analytes to the conductive polymer film. However, the Payne device requires high frequencies ranging from 100 MHz to 500 MHz, where the resonance may occur. The high frequency brings significant difficulties in sensor manufacturing and application. In addition, it still has the disadvantages inherent from polymer films.
In order to overcome deficiencies of the Payne technologies and invent a new sensor in the single sensor configuration with applying multiple frequency technology and vector analysis, the '425 Sun patent discloses a sensor serving as an analytical sensor for detecting and identifying analytes in fluids. The sensor is constructed from applying a pair of electrodes, wherein between the electrodes there are no additional materials designated to adsorb analytes if their concentrations are high, or there are adsorbents if the analyte concentrations are low. An alternating current voltage of varying frequencies is applied to the sensor by an alternating current device. In return, it detects electrical properties such as impedance and its components, reactance, resistance, and phase angles of the sensor with a subject of an analyte in a fluid when the subject resides in or passes through the electrodes at each frequency. Thus two spectra of electrical properties of the analyte can be established at various applied frequencies from a single measurement. The electrical properties are analyzed by a pattern recognition process, and compared with those of the known objects. Therefore, the analyte can be detected and identified. A reference sensor is provided with the same configuration of the analytical sensor. By combining electrical properties from the analytical and reference sensors, the '425 Sun patent provides a number of advantages, including selective detection of analytes of interest, and elimination of background effect including humidity influence, polymer film aging effect, and electrical property variations caused by the temperature variations.
The '763 Sun patent discloses various methods according to the disclosure of the '425 Sun patent, including for identifying analytes in fluids, detecting analytes in chromatography, and detecting hydrogen gases.
It will be appreciated that although the '425 and '763 Sun patents successfully disclose the sensor technology having two spaced apart electrodes in the single sensor configuration, there is stall a room for improving the sensor regarding its electrical characteristics, and output that is fundamental of the detection technology. This is because the output of the sensor is limited by the only one available gap between two electrodes, which are electrically polarized according to the alternative electrical polarities of the applied AC excitation. Therefore, the two electrodes alternatively having the different electrical polarities are exposed to an electrical environment that surrounds the sensor, so that there is a great chance for a cross talk between the sensor and surrounding electrical environment if the sensor is not electrically shielded.
Therefore, the present invention desires to develop a sensor including method that overcomes the disadvantages of conventional sensors, and has a better reproducibility of performance and sensor manufacturing, fewer interference deficiencies, enhanced sensitivities, less restricted operation conditions, increased portabilities, improved output and electrical, characteristics.